Hydrocephalus is a serious neurological disorder which was first described by Hippocrates (460–370 BC) as water on the brain. The disorder is characterized by an abnormal accumulation of cerebrospinal fluid in the brain’s ventricles and in pediatric cases often by an increased intracranial pressure. Currently, the general medical community consensus is that hydrocephalus is a heterogeneous group of disorders, rather than a single disease entity, and therefore the pathophysiology of hydrocephalus is much more complex and obscure than the clinical or radiological presentation of hydrocephalus (going beyond simply ventricular dilatation). Together with gross macroscopic changes, hydrocephalus results in significant changes to the brain tissue, not only of its morphology, but also of its dynamics, biochemistry, metabolism, and maturation. Successful treatment does not always reverse the injuries caused by hydrocephalus—early therapeutic intervention plays a crucial role in determining the reversibility of lesions, and, hence, the overall outcome. Realistic biomechanical models of hydrocephalus could advance our understanding about the pathophysiology of hydrocephalus and play an important role in predicting the evolution of hydrocephalus as well as the outcome of its treatment. In this chapter we will provide some basic facts about brain anatomy and mechanisms involved in the onset and evolution of hydrocephalus, and review some of the mathematical models of hydrocephalus currently in the literature.